P1021: JAKTINIB IN PATIENTS WITH MYELOFIBROSIS WHO WERE INTOLERANT TO RUXOLITINIB: AN OPEN-LABEL, SINGLE-ARM PHASE 2B STUDY
Authors: Yi Zhang, Hu Zhou, Zhijian Xiao, Minghui Duan, Sujun Gao, Guangsheng He, Hongmei Jing, Junmin LI, Liangming MA, Huanling Zhu, Chunkang Chang, Xin Du, Mei Hong, Xin LI, Qingchi Liu, Wei Wang, Xu Na, Haiping Yang, Qingwei Zhao, Jie Jin
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: As the first approved Janus kinase inhibitor (JAKi) for patients with symptomatic myelofibrosis (MF), ruxolitinib showed superiority in spleen volume reduction with increased anemia and thrombocytopenia. However, there are few treatment options after ruxolitinib intolerance. Jaktinib, an oral novel JAK and ACVR1 inhibitor showed promising efficacy in JAKi-naïve patients with intermediate or high risk MF with mild side effects. Aims: We conducted a single-arm phase 2b study to evaluate jaktinib in MF patients who were intolerant to ruxolitinib. Here we present the results of the cohort of patients who received jaktinib 100 mg twice a day. Methods: Patients who had primary, post-polycythemia vera or post-essential thrombocythemia MF and were previously treated with ruxolitinib for ≥28 days who either required red blood cell (RBC) transfusions or required more frequent transfusions on ruxolitinib, or had grade 3/4 anemia, thrombocytopenia or hematoma when receiving ruxolitinib, and with palpable spleen ≥5 cm were included. Patients were excluded from the study if they had received ruxolitinib ≥20 mg Bid for at least three months and were refractory or relapsed to ruxolitinib. The primary endpoint was the proportion of patients with spleen volume reduction of ≥35% from baseline (SVR35) at week 24, assessed by Independent Review Committee on the basis of MRI/CT images. Secondary endpoints included the best spleen response rate (defined as achieving SVR35 at any time), the proportion of patients with ≥50% reduction in MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS), anemia response, safety, etc. Results: In the full analysis set for efficacy, a total of 44 patients received jaktinib 100 mg twice daily and had completed the 24-week treatments and evaluations or terminated prior to week 24. In addition, one patient was excluded from the efficacy analysis due to incorrect diagnosis of MF but included in the safety analysis. The median baseline TSS was 9.5, hemoglobin was 80 g/L, and platelet count was 132.5×109/L. Patient baseline characteristics are summarized in the Table 1. While on ruxolitinib, 21 patients (47.7%) required RBC transfusion and all patients experienced grade 3/4 anemia, thrombocytopenia or both.The SVR35 rate at week 24 was 43.2% (19/44). Over the study phase, the best spleen response rate was 54.5% (24/44). The median time to achieve the first SVR35 was 12.1 weeks. Spleen response was maintained in 80.4% patients for at least 24 weeks and median duration was not reached. At week 24, 61.8% of the evaluable patients achieved a ≥50% improvement in TSS from baseline. Of 31 transfusion-independent patients with hemoglobin ≤100 g/L at baseline, 13 (41.9%) had an increase of hemoglobin ≥20 g/L by week 24. Of 19 patients who required RBC transfusion at baseline, 11 (57.9%) had a 50% decrease in RBC infusion frequency by week 24. Of nine transfusion-dependent patients at baseline, one became transfusion-independent by week 24. In the safety set (n=45), the median jaktinib exposure time was 280 days. The most common grade ≥3 treatment-related adverse events (TEAEs) were anemia (31.1%, n=14), thrombocytopenia (22.2%, n=10), pneumonia (17.8%, n=8), neutropenia (15.6%, n=7) and leukopenia (15.6%, n=7). Treatment discontinuation due to TEAEs occurred in five patients (11.1%). A dose reduction or temporary interruption due to TEAEs were reported in 12 patients (26.7%). Summary/Conclusion: Jaktinib demonstrated promising therapeutic activities in MF patients intolerant to ruxolitinib. Jaktinib 100 mg bid taken orally, not only substantially reduced splenomegaly, but also ameliorated MF-related symptom burdens and anemia. Jaktinib could be a new treatment for patients with anemia after ruxolitinib. Keywords: Janus Kinase inhibitor, Myeloproliferative disorder, Phase II, Myelofibrosis